α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling
α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling
复制标题
DOI：
10.1158/0008-5472.can-09-1462
复制
发表时间：
2010-01-01
期刊：
影响因子：
11.2
通讯作者：
Birkenmeier, Gerd
中科院分区：
文献类型：
--
作者：
Lindner, Inge;Hemdan, Nasr Y. A.;Birkenmeier, Gerd
确定可以改善脑肿瘤治疗的目标仍然很重要。这项对 α2-巨球蛋白 (A2M*) 转化相关亚型及其与低密度脂蛋白受体相关蛋白 1 (LRP1) 相互作用的研究提出了一种消除星形细胞瘤细胞恶性潜能的新机制。 LRP1 结合 A2M* 被发现与抑制肿瘤细胞增殖、迁移、侵袭、球状体形成和不依赖贴壁的生长有关。转录研究表明对 Wnt/β-连环蛋白信号通路的影响。值得注意的是，LRP1 抗体可以模拟 A2M* 的作用。我们的研究结果表明星形细胞瘤中的肿瘤抑制途径可能易于治疗开发。癌症研究； 70(1)； 277-87。 (C)2010 AACR。
Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of alpha 2-macroglobulin (A2M*) and its interaction with the low-density lipoprotein receptor-related protein-1 (LRP1) suggests a new mechanism for abrogating the malignant potential of astrocytoma cells. LRP1 bound A2M* found to be associated with an inhibition of tumor cell proliferation, migration, invasion, spheroid formation, and anchorage-independent growth. Transcriptional studies implicated effects on the Wnt/beta-catenin signaling pathway. Notably, LRP1 antibodies could phenocopy the effects of A2M*. Our findings suggest a pathway of tumor suppression in astrocytoma that might be tractable to therapeutic exploitation. Cancer Res; 70(1); 277-87. (C)2010 AACR.